Immunoglobulin E-Binding Structures on Antigen-Presenting Cells Present in Skin and Blood

Abstract

In atopic individuals, cutaneous antigen-presenting cells (APC), i.e., Langerhans cells and dermal dendritic cells, frequently display anti-IgE reactivity. Although earlier observations suggested that this phenomenon results from the binding of (complexed) IgE to the low-affinity IgE receptor (Fc epsilon RII/CD23), we and others demonstrated recently that Langerhans cells, dermal dendritic cells, and peripheral blood monocytes from atopic individuals can bind monomeric IgE via the high-affinity receptor for IgE (Fc epsilon RI). These new observations re-stimulated investigations aiming to unravel the nature and functionality of the relevant in vivo IgE-binding moiety(-ies) on APC. New data demonstrate that Fc epsilon RI, both quantitatively and qualitatively, is the pivotal serum IgE-binding structure on APC of atopics and, even more important, that Fc epsilon RI on APC functions as an allergen-focusing molecule. Thus, it is likely that allergens may be more efficiently taken up, processed, and presented to T cells after targeting to APC via Fc epsilon RI as compared with allergen binding to APC in the conventional manner. In vivo, Fc epsilon RI-IgE-dependent allergen presentation may critically lower atopic individuals' threshold to mount allergen-specific T-cell responses. This would result in the perpetuation of allergen-specific IgE production (type I reactions) and perhaps even the occurrence of T-cell-mediated, delayed-type hypersensitivity reactions in allergen-exposed tissues.